A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cell line derived from cultured tumor cells.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Peptides composed of between two and twelve amino acids.
A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Established cell cultures that have the potential to propagate indefinitely.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
Transport proteins that carry specific substances in the blood or across cell membranes.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
Physiologically inactive substances that can be converted to active enzymes.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
A subclass of caspases that contain short pro-domain regions. They are activated by the proteolytic action of INITIATOR CASPASES. Once activated they cleave a variety of substrates that cause APOPTOSIS.
Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.
A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.
Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.
A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
Elements of limited time intervals, contributing to particular results or situations.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Glycoproteins found on the membrane or surface of cells.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).
Proteins prepared by recombinant DNA technology.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A RIP serine-theonine kinase that contains a C-terminal caspase activation and recruitment domain. It can signal by associating with other CARD-signaling adaptor proteins and INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.
The action of a drug in promoting or enhancing the effectiveness of another drug.
A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Compounds that inhibit cell production of DNA or RNA.
A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
Proteins found in any species of virus.
The process of cleaving a chemical compound by the addition of a molecule of water.
A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Preparations of cell constituents or subcellular materials, isolates, or substances.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
Adenine nucleotides which contain deoxyribose as the sugar moiety.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Proteins found in any species of insect.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of MITOCHONDRIAL ADP, ATP TRANSLOCASES. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
The process by which chemical compounds provide protection to cells against harmful agents.
One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.
A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.
An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.
A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.

MycN sensitizes neuroblastoma cells for drug-induced apoptosis. (1/2233)

Amplification of the MYCN gene is found in a large proportion of neuroblastoma and considered as an adverse prognostic factor. To investigate the effect of ectopic MycN expression on the susceptibility of neuroblastoma cells to cytotoxic drugs we used a human neuroblastoma cell line harboring tetracycline-controlled expression of MycN. Neither conditional expression of MycN alone nor low drug concentrations triggered apoptosis. However, when acting in concert, MycN and cytotoxic drugs efficiently induced cell death. Apoptosis depended on mitochondrial permeability transition and activation of caspases, since the mitochondrion-specific inhibitor bongkrekic acid and the caspase inhibitor zVAD-fmk almost completely abrogated apoptosis. Loss of mitochondrial transmembrane potential and release of cytochrome c from mitochondria preceded activation of caspase-8 and caspase-3 and cleavage of PARP. CD95 expression was upregulated by treatment with cytotoxic drugs, while MycN cooperated with cytotoxic drugs to increase sensitivity to CD95-induced apoptosis and enhancing CD95-L expression. MycN overexpression and cytotoxic drugs also synergized to induce p53 and Bax protein expression, while Bcl-2 and Bcl-X(L) protein levels remained unchanged. Since amplification of MYCN is usually associated with a poor prognosis, these findings suggest that dysfunctions in apoptosis pathways may be a mechanism by which MycN-induced apoptosis of neuroblastoma cells is inhibited.  (+info)

Identification of an endogenous dominant-negative short isoform of caspase-9 that can regulate apoptosis. (2/2233)

Alternatively spliced isoforms of certain apoptosis regulators, such as Bcl-x, Ced-4, and Ich-1, have been shown to play opposing roles in regulating apoptosis. Here, we describe the identification of an endogenous alternatively spliced isoform of caspase-9, named caspase-9b, which lacks the central large subunit caspase domain. Caspase-9b is detectable in many cell lines by PCR and at the mRNA and protein levels. Caspase-9b can interact with the caspase recruitment domain of Apaf-1, and like the active site mutant of caspase-9, it can inhibit multiple forms of apoptosis, including those triggered by oligomerization of death receptors. It can also block activation of caspase-9 and -3 by Apaf-1 in an in vitro cytochrome c-dependent caspase activation assay. These results suggest that caspase-9b functions as an endogenous apoptosis inhibitory molecule by interfering with the formation of a functional Apaf-1-caspase-9 complex.  (+info)

Caspase-9 can be activated without proteolytic processing. (3/2233)

The recombinant form of the proapoptotic caspase-9 purified following expression in Escherichia coli is processed at Asp315, but largely inactive; however, when added to cytosolic extracts of human 293 cells it is activated 2000-fold in the presence of cytochrome c and dATP. Thus, the characteristic activities of caspase-9 are context-dependent, and its activation may not recapitulate conventional caspase activation mechanisms. To explore this hypothesis we produced recombinant forms of procaspase-9 containing mutations that disabled one or both of the interdomain processing sites of the zymogen. These mutants were able to activate downstream caspases, but only in the presence of cytosolic factors. The mutant with both processing sites abolished had 10% of the activity of wild-type, and was able to support apoptosis, with equal vigor to wild-type, when transiently expressed in 293 cells. Thus caspase-9 has an unusually active zymogen that does not require proteolytic processing, but instead is dependent on cytosolic factors for expression of its activity.  (+info)

Tumor necrosis factor alpha regulation of the FAS-mediated apoptosis-signaling pathway in synovial cells. (4/2233)

OBJECTIVE: Fas-mediated apoptosis is observed in synoviocytes of patients with rheumatoid arthritis (RA), but not in those of patients with osteoarthritis (OA). The present study was conducted to elucidate the mechanisms that initiate induction of Fas-mediated apoptosis in RA synoviocytes. METHODS: Cultured OA synoviocytes, which are insensitive to Fas-mediated apoptosis in spite of Fas antigen expression, were used in these experiments. Synovial cell proliferation and cytotoxicity studies were performed using MTS and lactate dehydrogenase release assays. Surface expression of Fas antigen was analyzed by flow cytometry. The expression and function of apoptosis-signaling molecules, such as caspase 8 and caspase 3, were examined by immunoblot analysis. RESULTS: Tumor necrosis factor alpha (TNFalpha) induced proliferation of cultured OA synoviocytes. Fas ligation with anti-Fas monoclonal antibody (mAb) resulted in cytotoxic activity against cultured OA synoviocytes that had been pretreated with TNFalpha for 5 days, but not those pretreated for 2 days. In contrast, anti-Fas mAb did not show a cytotoxic effect against untreated cultured OA synoviocytes. A gradual up-regulation of caspase 8 and caspase 3, which played a role in the caspase cascade for Fas-mediated apoptosis, was observed in TNFalpha-treated cultured OA synoviocytes. In addition, Fas ligation to TNFalpha-treated cultured OA synoviocytes induced activation of caspase 8 and caspase 3, with subsequent cleavage of poly(ADP-ribose) polymerase (PARP), a substrate of activated caspase 3. More importantly, Z-IETD-FMK, a caspase 8 inhibitor, and Ac-DEVD-CHO, a caspase 3 inhibitor, almost completely inhibited Fas-mediated apoptosis of TNFalpha-treated cultured OA synoviocytes, whereas Ac-YVAD-CHO, a caspase 1 inhibitor, did not. CONCLUSION: Our results clearly demonstrate that TNFalpha stimulates synovial cells to proliferate as well as sensitizes the cells for Fas-mediated apoptosis, at least in part by up-regulation and activation of caspase 8 and caspase 3. These findings suggest that TNFalpha may be one of the factors providing sensitization of synovial cells to Fas-mediated apoptosis in RA.  (+info)

Solution structure of BID, an intracellular amplifier of apoptotic signaling. (5/2233)

We report the solution structure of BID, an intracellular cross-talk agent that can amplify FAS/TNF apoptotic signal through the mitochondria death pathway after Caspase 8 cleavage. BID contains eight alpha helices where two central hydrophobic helices are surrounded by six amphipathic ones. The fold resembles poreforming bacterial toxins and shows similarity to BCL-XL although sequence homology to BCL-XL is limited to the 16-residue BH3 domain. Furthermore, we modeled a complex of BCL-XL and BID by aligning the BID and BAK BH3 motifs in the known BCL-XL-BAK BH3 complex. Additionally, we show that the overall structure of BID is preserved after cleavage by Caspase 8. We propose that BID has both BH3 domain-dependent and -independent modes of action in inducing mitochondrial damage.  (+info)

Solution structure of the proapoptotic molecule BID: a structural basis for apoptotic agonists and antagonists. (6/2233)

Members of the BCL2 family of proteins are key regulators of programmed cell death, acting either as apoptotic agonists or antagonists. Here we describe the solution structure of BID, presenting the structure of a proapoptotic BCL2 family member. An analysis of sequence/structure of BCL2 family members allows us to define a structural superfamily, which has implications for general mechanisms for regulating proapoptotic activity. It appears two criteria must be met for proapoptotic function within the BCL2 family: targeting of molecules to intracellular membranes, and exposure of the BH3 death domain. BID's activity is regulated by a Caspase 8-mediated cleavage event, exposing the BH3 domain and significantly changing the surface charge and hydrophobicity, resulting in a change of cellular localization.  (+info)

Nitric-oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome C release. (7/2233)

We have previously shown that nitric oxide (NO) stimulates apoptosis in different human neoplastic lymphoid cell lines through activation of caspases not only via CD95/CD95L interaction, but also independently of such death receptors. Here we investigated mitochondria-dependent mechanisms of NO-induced apoptosis in Jurkat leukemic cells. NO donor glycerol trinitrate (at the concentration, which induces apoptotic cell death) caused (1) a significant decrease in the concentration of cardiolipin, a major mitochondrial lipid; (2) a downregulation in respiratory chain complex activities; (3) a release of the mitochondrial protein cytochrome c into the cytosol; and (4) an activation of caspase-9 and caspase-3. These changes were accompanied by an increase in the number of cells with low mitochondrial transmembrane potential and with a high level of reactive oxygen species production. Higher resistance of the CD95-resistant Jurkat subclone (APO-R) cells to NO-mediated apoptosis correlated with the absence of cytochrome c release and with less alterations in other mitochondrial parameters. An inhibitor of lipid peroxidation, trolox, significantly suppressed NO-mediated apoptosis in APO-S Jurkat cells, whereas bongkrekic acid (BA), which blocks mitochondrial permeability transition, provided only a moderate antiapoptotic effect. Transfection of Jurkat cells with bcl-2 led to a complete block of apoptosis due to the prevention of changes in mitochondrial functions. We suggest that the mitochondrial damage (in particular, cardiolipin degradation and cytochrome c release) induced by NO in human leukemia cells plays a crucial role in the subsequent activation of caspase and apoptosis.  (+info)

Targeted disruption of caspase genes in mice: what they tell us about the functions of individual caspases in apoptosis. (8/2233)

Cysteine proteases of the caspase family are crucial mediators of apoptosis. All mammalian cells contain a large number of caspases. Although many caspases are activated in a cell committed to apoptosis, recent data from caspase gene knockout mice suggest that individual caspases may be involved in the cell and stimulus-specific pathways of cell death. The gene disruption studies also establish the functional hierarchy between two structurally distinct classes of caspases. The present review discusses these recent findings and elaborates on how these mutant mouse models have helped the understanding of the mechanisms that govern programmed cell death in the immune and other systems.  (+info)

Necrosis is a type of cell death that occurs when cells are exposed to excessive stress, injury, or inflammation, leading to damage to the cell membrane and the release of cellular contents into the surrounding tissue. This can lead to the formation of gangrene, which is the death of body tissue due to lack of blood supply.

There are several types of necrosis, including:

1. Coagulative necrosis: This type of necrosis occurs when there is a lack of blood supply to the tissues, leading to the formation of a firm, white plaque on the surface of the affected area.
2. Liquefactive necrosis: This type of necrosis occurs when there is an infection or inflammation that causes the death of cells and the formation of pus.
3. Caseous necrosis: This type of necrosis occurs when there is a chronic infection, such as tuberculosis, and the affected tissue becomes soft and cheese-like.
4. Fat necrosis: This type of necrosis occurs when there is trauma to fatty tissue, leading to the formation of firm, yellowish nodules.
5. Necrotizing fasciitis: This is a severe and life-threatening form of necrosis that affects the skin and underlying tissues, often as a result of bacterial infection.

The diagnosis of necrosis is typically made through a combination of physical examination, imaging studies such as X-rays or CT scans, and laboratory tests such as biopsy. Treatment depends on the underlying cause of the necrosis and may include antibiotics, surgical debridement, or amputation in severe cases.

1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

Neuroblastoma is caused by a genetic mutation that affects the development and growth of nerve cells. The cancerous cells are often sensitive to chemotherapy, but they can be difficult to remove surgically because they are deeply embedded in the nervous system.

There are several different types of neuroblastoma, including:

1. Infantile neuroblastoma: This type of neuroblastoma occurs in children under the age of one and is often more aggressive than other types of the cancer.
2. Juvenile neuroblastoma: This type of neuroblastoma occurs in children between the ages of one and five and tends to be less aggressive than infantile neuroblastoma.
3. Adult neuroblastoma: This type of neuroblastoma occurs in adults and is rare.
4. Metastatic neuroblastoma: This type of neuroblastoma has spread to other parts of the body, such as the bones or liver.

Symptoms of neuroblastoma can vary depending on the location and size of the tumor, but they may include:

* Abdominal pain
* Fever
* Loss of appetite
* Weight loss
* Fatigue
* Bone pain
* Swelling in the abdomen or neck
* Constipation
* Increased heart rate

Diagnosis of neuroblastoma typically involves a combination of imaging tests, such as CT scans and MRI scans, and biopsies to confirm the presence of cancerous cells. Treatment for neuroblastoma usually involves a combination of chemotherapy, surgery, and radiation therapy. The prognosis for neuroblastoma varies depending on the type of cancer, the age of the child, and the stage of the disease. In general, the younger the child and the more aggressive the treatment, the better the prognosis.

Within caspase-9's active site, in order for catalytic activity to occur there has to be specific amino acids in the right ... Caspase 8, NLRP1, and XIAP. The Proteolysis Map Caspase Caspase-3 Apoptosome Apaf-1 GRCh38: Ensembl release 89: ENSG00000132906 ... Similar to other caspases, caspase-9 has three domains: N-terminal pro-domain, large subunit, and a small subunit. The N- ... The introduction of caspases may also have medical benefits. In the context of graft versus host disease, caspase-9 can be ...
... akin to caspase 9's behaviour, an adequate enzymatic activity might demand the formation of a holoenzyme complex involving ... In Drosophila melanogaster cells, caspase Dronc is ubiquitylated by Diap-1. Similarly, effector caspases Caspase-3 and Caspase- ... In humans, initiator caspases such as Caspase-2 and Caspase-9 have a prodomain that cleaves caspases to a holoenzyme complex in ... Although most human caspases are considered orthologs of caspase Dronc, the one that resembles it the most is Caspase-2. ...
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs ... As an executioner caspase, the caspase-3 zymogen has virtually no activity until it is cleaved by an initiator caspase after ... Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. Caspase-3, in particular, (also ... During the caspase cascade, however, caspase-3 functions to inhibit XIAP activity by cleaving caspase-9 at a specific site, ...
The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and ... Caspase 7 has been shown to interact with: Caspase 8, Survivin and XIAP. The Proteolysis Map Caspase GRCh38: Ensembl release 89 ... Caspases exist as inactive proenzymes that undergo proteolytic processing by upstream caspases (caspase-8, -9) at conserved ... Caspase-7 is a member of the caspase (cysteine aspartate protease) family of proteins, and has been shown to be an executioner ...
... -1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'. Caspase-1 is key in activating pro- ... Caspase 10) Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) Once initiator caspases are activated, they produce a ... Apoptopic caspases are subcategorised as: Initiator Caspases (Caspase 2, Caspase 8, Caspase 9, ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ...
CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. Caspase-3 is activated ... Larsen BD, Rampalli S, Burns LE, Brunette S, Dilworth FJ, Megeney LA (March 2010). "Caspase 3/caspase-activated DNase promote ... October 2005). "The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated ... "Entrez Gene: DFFB DNA fragmentation factor, 40kDa, beta polypeptide (caspase-activated DNase)". Davidson College. "Caspase ...
... has a similar amino acid sequence to initiator caspases, including caspase 1, caspase 4, caspase 5, and caspase 9. It ... Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction. Caspase 2 has ... Within this family, caspase 2 is part of the Ich-1 subfamily. It is one of the most conserved caspases in different species of ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ...
... hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner". The Journal of Cell Biology. ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ... The protein was identified in the lab of Xiaodong Wang as an activator of caspase-3 in the presense of cytochromeC and dATP. ...
2005) XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J 24: 645-655 ... 2006) The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem 281: 3254-3260 Pop C, ... His research focuses on proteases and their inhibitors in humans, with particular emphasis on the caspases of the apoptotic ... 2006) The apoptosome activates caspase-9 by dimerization. Mol Cell 22: 269-275 Eckelman BP, Salvesen GS. ( ...
Caspase recruitment domain-containing protein 9 is an adaptor protein of the CARD-CC protein family, which in humans is encoded ... "Entrez Gene: CARD9 caspase recruitment domain family, member 9". Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL ... CARD9 is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated ... Merriam S, Du MQ, Dyer MJ, Robison KE, DiStefano PS, Alnemri ES (December 2000). "CARD9 is a novel caspase recruitment domain- ...
Rho inactivation can activate caspase-3 and caspase-9; two key components of the apoptotic pathway. TcdA has been linked to ... 50 (7): 613-9. doi:10.1099/0022-1317-50-7-613. PMID 11444771. Kuehne SA, Cartman ST, Heap JT, Kelly ML, Cockayne A, Minton NP ( ... 62 (2): 384-9. doi:10.1128/IAI.62.2.384-389.1994. PMC 186119. PMID 8300199. Hecht G, Pothoulakis C, LaMont JT, Madara JL ( ... 458 (7242): 1176-9. Bibcode:2009Natur.458.1176L. doi:10.1038/nature07822. PMC 2679968. PMID 19252482. (Protein pages needing a ...
Caspase 3. Caspase 7, Caspase-9, Diablo homolog HtrA serine peptidase 2, MAGED1, MAP3K2, TAB1, and XAF1. GRCm38: Ensembl ... Caspases are the enzymes primarily responsible for cell death. XIAP binds to and inhibits caspase 3, 7 and 9. The BIR2 domain ... When inhibiting caspase-3 and caspase-7 activity, the BIR2 domain of XIAP binds to the active-site substrate groove, blocking ... This allows normal caspase activity to proceed. The binding process of Smac/DIABLO to XIAP and caspase release requires a ...
... is one of the most studied ligands for HAVCR2 (TIM-3) and is expressed on various tumor cells. However, it can also ... Human galectin-9 is encoded by the LGALS9 gene. The protein has N- and C- terminal carbohydrate-binding domains connected by a ... Zhang ZY, Dong JH, Chen YW, Wang XQ, Li CH, Wang J, Wang GQ, Li HL, Wang XD (2012). "Galectin-9 acts as a prognostic factor ... 272 (9): 6078-86. doi:10.1074/jbc.272.9.6078. PMID 9038233. Türeci O, Schmitt H, Fadle N, Pfreundschuh M, Sahin U (March 1997 ...
Weng C, Li Y, Xu D, Shi Y, Tang H (Mar 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related ... Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological ... "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proceedings of the National Academy of ... 12 (9): 1432-40. doi:10.1210/mend.12.9.0166. PMID 9731710. Ray R, Chen G, Vande Velde C, Cizeau J, Park JH, Reed JC, Gietz RD, ...
The NLRP1 protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to ... responsible for the recruitment and activation of pro-caspase-1 in the active form of caspase-1. Human NLRP1 activation can be ... NLRP1 has been shown to interact with caspase 9 and APAF1. Via its FIIND domain, NLRP1 interacts directly with DPP9 and DPP8 ... Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The ...
In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. AIFM1 also ... a novel caspase-independent death effector released from mitochondria". Biochimie. 84 (2-3): 215-22. doi:10.1016/S0300-9084(02) ... "Mitochondrial release of caspase-2 and -9 during the apoptotic process". The Journal of Experimental Medicine. 189 (2): 381-94 ... "The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway". Cell Death and ...
Pan G, O'Rourke K, Dixit VM (1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". J. Biol. Chem. 273 (10): 5841-5. ... The mouse counterpart of this protein is found to interact with Apaf1 and forms a protein complex with Caspase 9, which ... 8 (2): 83-9. doi:10.1007/s101470300015. PMID 12720100. S2CID 24180107. Kang Y, Lee DC, Han J, et al. (2007). "NM23-H2 involves ... 87 (9): 923-40. doi:10.1007/s00109-009-0495-7. PMID 19551325. S2CID 23491033. BCL2L10 human gene location in the UCSC Genome ...
Murine caspase-11, and its human homologs caspase-4 and caspase-5, are mammalian intracellular receptor proteases activated by ... Caspase-11 activation by direct binding to LPS represents a novel and unprecedented mechanism for caspase activation. Caspase- ... "Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions". The Journal of Cell ... an inactive precursor to active caspase-11) expression and caspase-11-mediated pyroptosis. Once expressed, caspase-11 is only ...
Instead, it is thought to inhibit Caspase-1 activation by interfering with the interaction of Caspase-1 with other important ... and a caspase, in this case Caspase-1. In some cases, where the signaling proteins contain their own CARDs, like in NLRP1 and ... Caspase-1 is produced as a zymogen that can then be cleaved into 20 kDa (p20) and 10 kDa (p10) subunits that become part of the ... Active Caspase 1 contains two heterodimers of p20 and p10. It contains a catalytic domain with an active site that spans both ...
... antagonizes both the precursor and mature forms of Smac and caspase-9". J. Biol. Chem. 280 (1): 174-82. doi:10.1074/jbc. ... "Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function". Nat. Cell Biol. 6 (9): 849-60. doi: ... 6 (9): 791-806. doi:10.1101/gr.6.9.791. PMID 8889548. Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O (2000). " ... 9 (3): 99-106. doi:10.1093/dnares/9.3.99. PMID 12168954. Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, ...
Bonfoco E, Li E, Kolbinger F, Cooper NR (August 2001). "Characterization of a novel proapoptotic caspase-2- and caspase-9- ... Proteomics-based identification of proapoptotic caspase adapter protein as a novel serum marker of non-small cell lung cancer ... 54 (9): 2368-80. doi:10.1007/s00125-011-2212-7. PMID 21688198. Flach H, Rosenbaum M, Duchniewicz M, Kim S, Zhang SL, Cahalan MD ... 99 (9): 6398-403. Bibcode:2002PNAS...99.6398V. doi:10.1073/pnas.082112699. PMC 122960. PMID 11972030. ...
In addition, several other molecules, most notably caspase-3, have been reported to co-purify with the apoptosome and caspase-3 ... Another targeted molecule for cancer therapy involves the caspase family and their regulators. The inhibition of caspase ... this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. The term ... "Caspase-8 and Apaf-1-independent caspase-9 activation in Sendai virus-infected cells". The Journal of Biological Chemistry. 277 ...
The Patched dependence receptor triggers apoptosis through a DRAL-caspase-9 complex. », Nat Cell. Biol, 2009 Furne et al., « ...
"US Patent Application for COMBINATION THERAPIES USING CASPASE-1 DEPENDENT ANTICANCER AGENTS AND PGE2 ANTAGONISTS Patent ... 56 (9): 3467-3477. doi:10.1021/jm400351a. PMC 4059180. PMID 23594271. "National Academy of Inventors". (Articles with short ... More recently his work has shown that DPP8/9 inhibitors trigger an immune response. He also designed, synthesized, and ... "DPP8/9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis". Nature Chemical Biology. 13 (1): 46-53. ...
Marisol Soengas; Alarcón RM; Yoshida H; Giaccia AJ; Hakem R; Mak TW; Lowe SW (1 April 1999). "Apaf-1 and caspase-9 in p53- ...
"Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity". Experimental Cell Research ... 61 (8): 3443-9. PMID 11309306. Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ (October 2001). "Use of chromatin ... doi:10.1016/S0896-6273(02)00861-9. PMID 12372286. S2CID 10534933. Song H, Xia SL, Liao C, Li YL, Wang YF, Li TP, Zhao MJ ( ... doi:10.1016/S0896-6273(02)00861-9. PMID 12372286. S2CID 10534933. Chang, Chunmei; Young, Lindsey N.; Morris, Kyle L.; von Bülow ...
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 10 has been shown to interact with FADD, CFLAR, Caspase 8, Fas receptor, RYBP, TNFRSF1A and TNFRSF10B. The Proteolysis ... Wang, J; Chun H J; Wong W; Spencer D M; Lenardo M J (November 2001). "Caspase-10 is an initiator caspase in death receptor ... This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene ...
... has been shown to interact with Caspase 8. The Proteolysis Map Caspase GRCh38: Ensembl release 89: ENSG00000138794 - ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative splicing of this gene ... "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase". Cowling V, Downward J (Oct 2002). "Caspase-6 is the direct ...
Gly Caspase-10 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-8 (EC 3.4.22.61) and caspase-9 (EC 3.4.22.62 ... Shikama Y, Yamada M, Miyashita T (July 2003). "Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK and IKKalpha ... Fischer U, Stroh C, Schulze-Osthoff K (January 2006). "Unique and overlapping substrate specificities of caspase-8 and caspase- ... Caspase-10 (EC 3.4.22.63, FLICE2, Mch4, CASP-10, ICE-like apoptotic protease 4, apoptotic protease Mch-4, FAS-associated death ...
This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... 1998). "Identification and characterization of murine caspase-14, a new member of the caspase family". Cancer Res. 58 (22): ... 2004). "Vitamin D3 induces caspase-14 expression in psoriatic lesions and enhances caspase-14 processing in organotypic skin ...
Src (gene) has been shown to interact with the following signaling pathways: PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL ... 10 (3): 1000-9. doi:10.1128/mcb.10.3.1000. PMC 360952. PMID 1689455. Zan L, Wu H, Jiang J, Zhao S, Song Y, Teng G, Li H, Jia Y ... There are 9 members part of the Src family kinases: c-Src, Yes, Fyn, Fgr, Yrk, Lyn, Blk, Hck, and Lck. The expression of these ... 58 (8): 872-9. doi:10.1016/j.neuint.2011.02.014. PMC 3100427. PMID 21334414. Zan L, Zhang X, Xi Y, Wu H, Song Y, Teng G, Li H, ...
Wang M, Qanungo S, Crow MT, Watanabe M, Nieminen AL (2005). "Apoptosis repressor with caspase recruitment domain (ARC) is ... NOL3 has been shown to interact with SFRS9 and Caspase 8. GRCh38: Ensembl release 89: ENSG00000140939 - Ensembl, May 2017 ... Ekhterae D, Platoshyn O, Zhang S, Remillard CV, Yuan JX (2003). "Apoptosis repressor with caspase domain inhibits cardiomyocyte ... "Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and ischemic ...
Granzymes usually cause apoptosis of the infected cell through initiation of the caspase cascade. However, apoptosis can also ... The 9 kDa form functions as a pore-forming protein, as it is able to permeabilize cell membranes.The 9kDa form can cytolyze ... The 9 kDa form is also inhibited by cholesterol which is present in usually present in mammalian cells, but not in most ... The 9 kDa form consists of 74 amino acids, and has a cytotoxic function. This molecule is found in cytotoxic granules, along ...
In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin- ... 24 (6): 352-9. doi:10.1016/j.tcb.2013.12.003. PMC 4037451. PMID 24457024. Goldberg, AL; Stein, R; Adams, J (August 1995). "New ... 139 (1): 47-9. doi:10.1016/0304-3940(92)90854-z. PMID 1328965. S2CID 28190967. Mathews, KD; Moore, SA (January 2003). "Limb- ... 111 (8): 2984-9. Bibcode:2014PNAS..111.2984P. doi:10.1073/pnas.1400546111. PMC 3939901. PMID 24516147. Rock KL, Gramm C, ...
... called Inhibitor of caspase-activated DNase (ICAD). In order for apoptosis to begin, an enzyme called caspase 3 cleaves ICAD so ... "Caspase-activated DNase Is Required for Maintenance of Tolerance to Lupus Nuclear Autoantigens." Arthritis and Rheumatism 64.4 ... Apoptotic DNA fragmentation relies on an enzyme called Caspase-Activated DNase (CAD). CAD is usually inhibited by another ... "Identification of ICAD-derived Peptides Capable of Inhibiting Caspase-activated DNase." FEBS Journal 279.16 (2012): 2917-928. ...
"Relationship between Caspase Activity and Apoptotic Markers in Human Sperm in Response to Hydrogen Peroxide and Progesterone". ... 44 (9): 959-68. doi:10.1177/44.9.8773561. PMID 8773561. Negoescu A, Guillermet C, Lorimier P, Brambilla E, Labat-Moleur F (1998 ...
If cells receive multiple apoptotic stimuli, caspase-3 activates the Mst1 kinase, which phosphorylates the serine at position ... ISBN 978-1-4292-3413-9. Molden RC, Bhanu NV, LeRoy G, Arnaudo AM, Garcia BA (2015). "Multi-faceted quantitative proteomics ... 279 (1-2): 133-9. doi:10.1007/s11010-005-8285-1. PMID 16283522. S2CID 25071586. R, Fujiki; W, Hashiba; H, Sekine; A, Yokoyama; ...
Hayashi Y, Arakaki R, Ishimaru N (2003). "The role of caspase cascade on the development of primary Sjögren's syndrome". J. Med ... 8 (1): 1-9. doi:10.1128/MCB.8.1.1. PMC 363070. PMID 3336352. Leto, T. L.; Fortugno-Erikson, D.; Barton, D.; Yang-Feng, T. L.; ... 8 (1): 1-9. doi:10.1128/MCB.8.1.1. PMC 363070. PMID 3336352. McMahon AP, Giebelhaus DH, Champion JE, Bailes JA, Lacey S, ... 48 (6): 1050-9. doi:10.1016/j.yjmcc.2010.01.001. PMC 3537504. PMID 20114050. Cianci CD, Zhang Z, Pradhan D, Morrow JS (Nov 1999 ...
Costanzo A, Guiet C, Vito P (1999). "c-E10 is a caspase-recruiting domain-containing protein that interacts with components of ... 8 (2): 113-6. doi:10.1016/S0960-9822(98)70042-9. PMID 9427646. S2CID 6269984. Chaudhary PM, Eby M, Jasmin A, Bookwalter A, ... doi:10.1016/S0092-8674(00)81265-9. PMID 8681376. S2CID 7415784. Takeuchi M, Rothe M, Goeddel DV (1996). "Anatomy of TRAF2. ...
... activate inflammatory caspases (e.g. caspase 1) causing cleavage and activation of important inflammatory cytokines such as IL- ... Other NLRs such as IPAF and NAIP5/Birc1e have also been shown to activate caspase-1 in response to Salmonella and Legionella. ... 6 (1): 9-20. doi:10.1038/nri1747. PMID 16493424. S2CID 33505741. Burberry A, Zeng MY, Ding L, Wicks I, Inohara N, Morrison SJ, ... 13 (9): 817-822. doi:10.1038/ni.2369. PMC 3432564. PMID 22910394. Cummings RD, McEver RP (2009). "C-type Lectins". In Varki A, ...
In cells, Bcl-rambo is localized to the mitochondria, and its overexpression induces apoptosis that is blocked by caspase ... 586 (19): 3142-9. doi:10.1016/j.febslet.2012.08.015. PMID 22921587. S2CID 31709574. * Yi P, Zhang W, Zhai Z, Miao L, Wang Y, Wu ...
In one such pathway, caspase-independent apoptosis, the E3 ligase C-terminal of Hsc-70 interacting protein (CHIP), a regulator ... Lemarié A, Lagadic-Gossmann D, Morzadec C, Allain N, Fardel O, Vernhet L (Jun 2004). "Cadmium induces caspase-independent ... This protein primarily participates in caspase-independent apoptosis via DNA degradation when translocating from the ... Differential involvement of caspase-3 and endonuclease G". Journal of Neurovirology. 10 (3): 141-51. doi:10.1080/ ...
Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis- ... 3 (9): 839-43. doi:10.1038/ncb0901-839. PMID 11533664. S2CID 21164493. Zhang B, Rong R, Li H, Peng X, Xiong L, Wang Y, Yu X, ... 14 (6): 450-9. doi:10.1038/sj.cr.7290247. PMID 15625011. S2CID 21654486. Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE ... 11 (3): 1793-9. doi:10.3892/mmr.2014.2939. PMC 4270332. PMID 25394481. Zhang P, Leu JI, Murphy ME, George DL, Marmorstein R ( ...
It has also been suggested that S1P kinase 2 (SphK2) is a target of caspase 1, and that a cleaved fragment of SphK2 is what is ... In other forms of apoptosis, caspase-1 is not normally induced, meaning the formation of S1P needs to be further studied. S1P ... S1P generation involved caspase-1-dependent release of sphingosine kinase 2 (SphK2) fragments. CX3CL1 release is mediated ... Release is dependent upon caspase activity. Less than 2% of ATP released from the beginning stages of cell death is released ...
2006). "Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway". Oncogene. 25 (30): 4172-82. doi:10.1038/ ... and it plays a role in the increase of cell survival in a caspase 3 dependent pathway. GRCh38: Ensembl release 89: ... 20 (39): 5562-9. doi:10.1038/sj.onc.1204726. PMID 11571656. Bailey SD, Xie C, Do R, et al. (2010). "Variation at the NFATC2 ...
Her demonstration that caspases are involved directly in ischaemic brain damage in vivo stimulated the development of caspase ... Retrieved 9 March 2016.{{cite web}}: CS1 maint: bot: original URL status unknown (link) "Royal Society Africa Prize - Royal ...
... mitochondrial dysfunction and caspase-3-dependent signaling pathways". International Journal of Oncology. 39 (1): 217-224. doi: ... 64 (9): 1415-24. doi:10.1016/s0006-2952(02)01347-3. PMID 12392823. Ramachandran Nair AG; Joshi BS (October 1979). "Oroxindin-A ... 574 (2-3): 112-9. doi:10.1016/j.ejphar.2007.07.011. PMID 17692312. v t e (Articles with changed EBI identifier, Articles with ...
... encoding protein Caspase 16, pseudogene CCDC113: encoding protein Coiled-coil domain-containing protein 113 Ccdc78: encoding ... 24 (9): 1329-1350. doi:10.1038/s41380-018-0025-5. PMC 6756231. PMID 29467497. Genome Decoration Page, NCBI. Ideogram data for ...
The long NALP, NALP1 (MIM 606636), also has a C-terminal extension containing a function to find domain (FIIND) and a caspase ... 2002). "Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1". ... a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing ... recruitment domain (CARD). NALPs are implicated in the activation of proinflammatory caspases (e.g., CASP1; MIM 147678) via ...
... the apoptotic effector caspase, caspase 3, cleaves ICAD and thus causes CAD to become activated. CAD cleaves the DNA at the ... The enzyme responsible for apoptotic DNA fragmentation is the Caspase-activated DNase. CAD is normally inhibited by another ... "A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD". Nature. 391 (6662): 43-50. Bibcode: ... doi:10.1016/0022-2836(70)90277-9. PMID 5481278. Quail, Michael Andrew (2010). "DNA: Mechanical Breakage". Encyclopedia of Life ...
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"Induction of Caspase-9, Biochemical Assessment and Morphological Changes Caused by Apoptosis in Cancer Cells Treated with ... The cream-colored inner petals are 7-15 by 4-9 millimeters and have a 1.3-2.1 millimeter wide claw. The outer surface of the ...
The long NALP, NALP1 (MIM 606636), also has a C-terminal extension containing a function to find domain (FIIND) and a caspase ... a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing ... 179 (9): 6291-6. doi:10.4049/jimmunol.179.9.6291. PMID 17947705. Chen L, Wilson JE, Koenigsknecht MJ, et al. (2017). "NLRP12 ... recruitment domain (CARD). NALPs are implicated in the activation of proinflammatory caspases (e.g., CASP1; MIM 147678) via ...
Mukerjee N, McGinnis KM, Gnegy ME, Wang KK (August 2001). "Caspase-mediated calcineurin activation contributes to IL-2 release ... 142 (5): 1752-9. doi:10.1210/endo.142.5.8156. PMID 11316738. Graef IA, Chen F, Chen L, Kuo A, Crabtree GR (June 2001). "Signals ... 285 (5): 1192-9. CiteSeerX 10.1.1.414.4108. doi:10.1006/bbrc.2001.5278. PMID 11478781. Volkel H, Scholz M, Link J, Selzle M, ... 9 (11): 1681-90. doi:10.1093/hmg/9.11.1681. PMID 10861295. Frey N, Richardson JA, Olson EN (December 2000). "Calsarcins, a ...
2003). "HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear ... 9 (11): 1172-84. doi:10.1038/sj.cdd.4401094. PMID 12404116. S2CID 38809690. Strausberg RL, Feingold EA, Grouse LH, et al. (2003 ...
... an investigational drug targeting caspases and caspase-like proteases: the clinical trials in sight and recent anti- ... May 2016). "The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute ... The substance acts as a pan-caspase inhibitor and has antiapoptotic and antiinflammatory effects. It was developed for the ... November 2005). "First-in-class pan caspase inhibitor developed for the treatment of liver disease". Journal of Medicinal ...
Caspase-3 (Pharmingen, San Diego, CA), caspase-8 (FADD-like interleukin-1 beta-converting enzyme) and caspase-9-like Mch6 (MBL ... The cell lysates (100 μg/100 μl protein) were incubated with specific substrate Ac-DEVD-AMC for caspase-3, IETD-pNA for caspase ... Apoptosis-mediated enhancement of DNA-raised immune responses by mutant caspases. Nat Biotechnol. 2001;19:543-7. DOIPubMed ... The DN caspase-9 specifically blocked the cleavage of pro-caspase-9 in pcWNV-Cp-DJY and pcWNV-CpWT cotransfected cell lysates ...
The obtained results show that the designed biosensor detects the caspase-9 activity in the cell-free and cell-based systems. ... In this project, a luciferase-based biosensor for detecting and measuring caspase-9 activity is designed and constructed using ... Afterward, the biosensor is utilized for measuring the cellular caspase-9 activity upon apoptosis induction in a cancer cell ... Developing a circularly permuted variant of Renilla luciferase as a bioluminescent sensor for measuring Caspase-9 activity in ...
Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling. 30 March 2020 ... P , 0.05; **P , 0.01; ****P , 0.0001 (two-way ANOVA analysis). For a, n = 9 biologically independent mice in 22 °C, 30 °C and ... 9 biologically independent mice in all groups; For d and f, n = 8 biologically independent mice in Rad + 30 °C group, n = 10 ... 9 biologically independent mice in WT Rad + anti-CD8 and WT Rad + isotype groups, n = 8 biologically independent mice in KO Rad ...
Animals Antibodies Antigens, CD95 Apoptosis Caspase 1 Caspase 3 Caspase 9 Caspases Cells, Cultured Enzyme Activation Hemorrhage ... deficiency in caspases essential for this pathway, caspase-9 or caspase-3, unexpectedly resulted in rapid activation of ... we demonstrate here that elimination of certain caspases was compensated in vivo by the activation of other caspases. ... also elicited compensatory activation of caspases in cultured caspase-3(-/-) hepatocytes, indicating that the compensatory ...
Nod-1 was found to bind to multiple caspases with long prodomains, but specifically activated caspase-9 and promoted caspase- 9 ... Nod-1 was found to bind to multiple caspases with long prodomains, but specifically activated caspase-9 and promoted caspase- 9 ... Nod-1 was found to bind to multiple caspases with long prodomains, but specifically activated caspase-9 and promoted caspase- 9 ... Nod-1 was found to bind to multiple caspases with long prodomains, but specifically activated caspase-9 and promoted caspase- 9 ...
Ene AC, Park S, Edelmann W, Taketo T. Corrigendum to "Caspase 9 is constitutively activated in mouse oocytes and plays a key ... T1 - Corrigendum to "Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during ... Corrigendum to "Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during ... Corrigendum to "Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during ...
Antibody Details for Caspase 9/LAP6 Ab-2. WBI Title. Validation Status. Band Result. Date. Dilution. ... recombinant human caspase 9 prodomain. Caspase 9 prodomain. Homo Sapiens. *Homo Sapiens ...
Cited in 8 publications. View Rabbit Polyclonal anti-bcl-x Antibody [Unconjugated] (AF800). Validated Applications: WB, Simple Western, IP. Validated Species: Human, Mouse. Sample size available.
CARD11: caspase recruitment domain family member 11. *CARD14: caspase recruitment domain family member 14 ...
Expression of caspase-9 also increased within the first 3 h of infection, but subsequently decreased. Modulation of miR-4276 ... COX6C mRNA expression through silencing miR-4276 and repressed viral replication by inducing the apoptotic protein caspase-9. ...
MeSH Terms: Animals; Astrocytes/cytology; Astrocytes/drug effects*; Astrocytes/enzymology; Caspase 3/metabolism*; Caspase 9/ ... Title: Oxidative stress, caspase-3 activation and cleavage of ROCK-1 play an essential role in MeHg-induced cell death in ... MeHg also induced an increase in mitochondrial-dependent caspase-9 and caspase-3, while the levels of RhoA protein expression ... Inhibiting ROCK-1 and caspases activation attenuated the MeHg-induced cell death. Collectively, these findings are the first to ...
... effector caspases (i.e., caspase 6), and upregulates the levels of cleaved-caspase 6 (32). In the present study, the protein ... cleaved-caspase 6 and Bax. β-actin served as a loading control. (G) Relative protein expression levels of Bax, cleaved-caspase ... caspase 6 and cleaved‑caspase 9, in a dose‑dependent manner. Mechanistically, involucrasin A significantly inhibited the ... B-E) Protein expression levels of cleaved-caspase 9, cleaved-caspase 6, p-Akt, Akt, p-MDM2, MDM2, p53 and Bax were examined via ...
Under normal conditions, caspase-9 is believed to be primarily involved in programmed cell death, a tightly regulated mechanism ... The new treatment targets an enzyme called caspase-9, says Carol M. Troy, MD, PhD, professor of pathology & cell biology and of ... In studies of mice, the Troy lab discovered that when blood vessels are injured by retinal vein occlusion, caspase-9 becomes ... Eye drops with a caspase-9 inhibitor prevent retinal injury from retinal vein occlusion. In the left image, RVO causes swelling ...
Selenium activated caspases-1 and -12, whereas vitamin E activated caspase-9. Thus, selenium and vitamin E in combination may ... This synergy was accounted for primarily by selenium and vitamin E modifying distinct signaling pathways regulating caspase ... and caspase-3) pathways. The soy isoflavone daidzen has been reported to improve the capacity of tamoxifen to prevent mammary ... Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time. Email [email protected] ...
Active/Pro-Caspase 3 Recombinant Rabbit Monoclonal Antibody (SU38-04). Advanced Verification 1 Reference ...
Specifically, the XIAP protein inhibits caspase enzymes 3, 7, and 9. The XIAP protein also plays a role in several other ... the action of certain enzymes called caspases, which are necessary for apoptosis. ...
Caspase-9 transduction overrides the resistance mechanism against p53-mediated apoptosis in U87MG glioma cells. Neurosurgery. ... GBM Derived Gangliosides Induce T Cell Apoptosis through Activation of the Caspase Cascade Involving Both the Extrinsic and the ... 2019 Jan.1-9. Pubmedid: 30660120. *Huang RY, Bi WL, Griffith B, Kaufmann TJ, la Fougère C, Schmidt NO, Tonn JC, Vogelbaum MA, ... 2017 Sep.18(9):e508. Pubmedid: 28884696. *Sharma M, Jia X, Ahluwalia M, Barnett GH, Vogelbaum MA, Chao ST, Suh JH, Murphy ES, ...
Western blot of caspase-3, MLKL, Gasdermin D (Gsdm D) and H3Cit (g), LDH release (h) and Cell viability (i) in Padi4WT and ... Western blot of caspase 1, −3 and gasdermin D (Gsdm D) and H3Cit in 4T1 and RAW264.7 (j), LDH release (k) and cell viability (l ... 2. Caspases and calcium are necessary for apoptosis-induced nuclear expulsion. a, Percentage of Padi4WT and Padi4KO 4T1 cells ... a,b, Percentage of Padi4WT or Padi4KO H2B-GFP 4T1 with active caspase-3/7 (a) and with CitH3 positivity among cells showing ...
Kang SJ, Kim BM, Lee YJ, Hong SH, Chung HW (2009) Titanium dioxide nanoparticles induce apoptosis through the JNK/p38-caspase-8 ... c, binding with apoptotic protease activating factor 1 (Apaf-1), induces the caspase-dependent apoptosis. The increase of ROS ... This structure activates the initiator caspase-9 (CASP-9; EC 3.4.22.62) that subsequently activates the executioner caspase-3 ( ... Beclin 1 inhibits apoptosis by the inactivation of caspase-8 (CASP-8; EC 3.4.22.61), an enzyme transforming Bid to tBid, a pro- ...
Caspase-9 and caspase3 were also induced by the silica treatment. The results show that silica particles induce AM apoptosis ... Mitochondrial release of Cytochrome c and the resulting activation of caspase-9 and caspase-3 were determined by Western blots ... may activate caspase cascade leading to cell apoptosis. The purpose of this study is to investigate the potential involvement ... Page last reviewed: December 9, 2020 Content source: National Institute for Occupational Safety and Health Education and ...
caspase 1. multiple interactions. decreases activity. decreases expression. EXP. ISO. Minocycline inhibits the reaction [HTT ... caspase 3. decreases activity. multiple interactions. decreases expression. ISO. EXP. Minocycline results in decreased activity ... caspase 8. multiple interactions. decreases expression. EXP. Minocycline inhibits the reaction [HTT protein mutant form results ... caspase 9. decreases activity. multiple interactions. decreases expression. ISO. EXP. Minocycline results in decreased activity ...
Caspase-9 has a nonapoptotic function in Xenopus embryonic primitive blood. formation., Tran HT., J Cell Sci. July 15, 2017; ...
Caspase inhibitor z-LEHD-fmk acts as a selective caspase-9 inhibitor with anti-apoptotic properties. This drug helps decreasing ... Caspase inhibitor Z-DEVD-fmk is a selective caspase-3 inhibitor that also has anti-inflammatory properties. Anti-apoptosis ... caspase-1, and caspase-3. Moreover, minocycline enhances Bcl-2 and thus, reduces apoptosis, also, it decreases p38 mitogen- ... On the other hand, FK506 inhibits caspase-3 and NF-kB, improving functional recovery with the increase of rostral axonal ...
Experimental observations showed that UDA can induce cell apoptosis through a caspase 9-dependent pathway. The expression ...
Smac mimetic bypasses apoptosis resistance in FADD- or caspase-8-deficient cells by priming for tumor necrosis factor α-induced ... Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: Implications for Smac-dependent anti-apoptotic ... The Drosophila inhibitor of apoptosis D-IAP1 suppresses cell death induced by the caspase drICE ... Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf ...
Caspases [D12.776.476.075.405] * Caspases, Initiator [D12.776.476.075.405.550] * Caspase 1 [D12.776.476.075.405.550.100] ... Caspases [D08.811.277.656.262.500.126] * Caspases, Initiator [D08.811.277.656.262.500.126.550] * Caspase 1 [D08.811.277.656. ... Caspases [D08.811.277.656.300.200.126] * Caspases, Initiator [D08.811.277.656.300.200.126.550] * Caspase 1 [D08.811.277.656. ... A long pro-domain caspase that contains a CASPASE RECRUITMENT DOMAIN in its pro-domain region. Caspase 9 is activated during ...
  • Integration of GWAS and human kidney expression of quantitative trait analysis using Bayesian colocations, transcriptome-wide association studies, and summary-based Mendelian randomization studies prioritized caspase-9 (CASP9) as a kidney disease risk gene. (nih.gov)
  • Studies to date have shown the role of caspase-8 (CASP8) and caspase-9 (CASP9) in carcinogenesis. (nih.gov)
  • Influence of survivin (BIRC5) and caspase-9 (CASP9) functional polymorphisms in renal cell carcinoma development: a study in a southern European population. (cdc.gov)
  • This issue should therefore be considered in developing caspase inhibitors for therapeutic applications. (cshl.edu)
  • Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors. (nih.gov)
  • ghaffari moghadam M, abedi B, banaeifar A. The effect of high intensity interval training on the expression of Caspase 3 and 9 horseshoe protein genes in male rats. (ac.ir)
  • One-way analysis of variance to compare the expression of caspase 3 and 9 horseshoe protein in male rats in the three groups of high-intensity intermittent exercise, control and control of diabetic basal showed a significant difference between the three means of the group (p = 0.001). (ac.ir)
  • Rho-associated protein kinase 1 (ROCK-1) is a major downstream effector of the small GTPase RhoA and a direct substrate of caspase-3. (nih.gov)
  • MeHg also induced an increase in mitochondrial-dependent caspase-9 and caspase-3, while the levels of RhoA protein expression were reduced or unchanged. (nih.gov)
  • 1. Matrin 3 is a Ca2+/calmodulin-binding protein cleaved by caspases. (nih.gov)
  • 12. Specific proteolysis of the A-kinase-anchoring protein 149 at the Asp582 residue by caspases during apoptosis. (nih.gov)
  • Our data suggests that on initial exposure to influenza virus, host cells upregulate COX6C mRNA expression through silencing miR-4276 and repressed viral replication by inducing the apoptotic protein caspase-9. (cdc.gov)
  • Bcl-x is a pro-survival protein that opposes the pro-apoptotic action of Bax which interacts with mitochondria to activate the caspase 9 pathway. (nih.gov)
  • The team focused on another group of enzymes called caspases that are known to be important for inflammation and thus might also serve as useful therapeutic targets. (nih.gov)
  • It helps protect these cells from self-destructing (undergoing apoptosis) by blocking (inhibiting) the action of certain enzymes called caspases, which are necessary for apoptosis. (nih.gov)
  • 28. Reduction of miR-21 induces glioma cell apoptosis via activating caspase 9 and 3. (nih.gov)
  • L-asparaginase from human breast milk Lactobacillus reuteri induces apoptosis using therapeutic targets Caspase-8 and Caspase-9 in breast cancer cell line. (bvsalud.org)
  • We have previously shown that silica particles, a ubiquitous occupational fibrogenic agent that induces inflammatory responses through microtubule alterations, may activate caspase cascade leading to cell apoptosis. (cdc.gov)
  • Taken together, the p38-MAPK pathway is required in oridonin-induced pancreatic cancer cell apoptosis, and which is dependent on its downstream target p53 and caspase activation. (spandidos-publications.com)
  • deficiency in caspases essential for this pathway, caspase-9 or caspase-3, unexpectedly resulted in rapid activation of alternate caspases after injection of Jo2, and therefore failed to protect mice against Jo2 toxicity. (cshl.edu)
  • Moreover, both ultraviolet and gamma irradiation, two established inducers of the mitochondrial caspase-activation pathway, also elicited compensatory activation of caspases in cultured caspase-3(-/-) hepatocytes, indicating that the compensatory caspase activation was mediated through the mitochondria. (cshl.edu)
  • an expression level of pro-caspase-9 cleavage products (35-37 kD) was compared to 3′-terminal deletion mutant, pcWNV-Cp∆3′ (Cp∆3′) and pcDNA3.1 by Western blot analysis with anti-human caspase-9 mAb. (cdc.gov)
  • Oxidative stress, caspase-3 activation and cleavage of ROCK-1 play an essential role in MeHg-induced cell death in primary astroglial cells. (nih.gov)
  • 19. AlphaII-spectrin is an in vitro target for caspase-2, and its cleavage is regulated by calmodulin binding. (nih.gov)
  • This study aimed to induce apoptosis in breast cancer cells by purifying L- asparaginase from human breast milk Lactobacillus reuteri isolates via inhibition of Caspases 8 and 9. (bvsalud.org)
  • In additional experiments, the team found that the NSAID inhibition of caspase was independent of COX enzymes. (nih.gov)
  • The antiapoptotic effect of vitamin C was associated with reduced cytochrome C release from mitochondria and the inhibition of caspase-9 activity. (nih.gov)
  • Breast cancer cell line was used to study the effect of the enzyme on the caspase 8 and caspase 9 gene expression . (bvsalud.org)
  • The new treatment targets an enzyme called caspase-9, says Carol M. Troy, MD, PhD, professor of pathology & cell biology and of neurology in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Vagelos College of Physicians and Surgeons, who led the studies. (nih.gov)
  • The team first ranked the drugs by their ability to inhibit the activity of the caspase-4 enzyme. (nih.gov)
  • It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES . (nih.gov)
  • Caspases (CASPs) are the main executors of the apoptotic process. (nih.gov)
  • As effectors of the apoptotic machinery, caspases are considered potential therapeutic targets. (cshl.edu)
  • Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 . (nih.gov)
  • Mitochondrial release of Cytochrome c and the resulting activation of caspase-9 and caspase-3 were determined by Western blots. (cdc.gov)
  • In following the gene of biosensor is sub-cloned into a eukaryotic vector and transfected to HEK293T cell line and then its activity is measured upon apoptosis induction in the presence and absence of a caspase-9 inhibitor. (caltech.edu)
  • Furthermore, the activation of the p38 kinase promoted the activation of p53 and its downstream target p21, and further caused caspase-9 and -3 activation, as demonstrated by evidence showing that the p38 inhibitor SB203580 not only blocked the phosphorylation of p38 but also reduced the activation of p53, p21 and caspase-9 and -3. (spandidos-publications.com)
  • Importantly, a p38 inhibitor but neither an ERK inhibitor nor a JNK inhibitor, blocked the phosphorylation of p38 and also reduced the activation of p53, p21 and caspase-9 and -3. (spandidos-publications.com)
  • Eye drops with a caspase-9 inhibitor prevent retinal injury from retinal vein occlusion. (nih.gov)
  • Influence of caspases 8 and 9 gene promoter polymorphism on prostate cancer susceptibility and early development of hormone refractory prostate cancer. (cdc.gov)
  • Polymorphisms of caspase 8 and caspase 9 gene and colorectal cancer susceptibility and prognosis. (cdc.gov)
  • Caspase 8 and caspase 9 gene polymorphisms and susceptibility to gastric cancer. (cdc.gov)
  • NB100-56186) that we used for localizing XIAP does not recognize XIAP, but instead most likely recognizes the cleaved Caspase 9 which conjugates with XIAP in the apoptosome. (elsevierpure.com)
  • c , Colorimetric caspase-3 activity assay using pcWNV-Cp-DJY (Cp-DJY), pcWNV-CpWT (CpWT), or pcWNV-CpΔ3′ (CpΔ3') plasmid-transfected cells. (cdc.gov)
  • Under normal conditions, caspase-9 is believed to be primarily involved in programmed cell death, a tightly regulated mechanism for naturally eliminating damaged or excess cells. (nih.gov)
  • In human cells, the caspases were inhibited by the same NSAIDs in the same rank order as in the high-throughput screen. (nih.gov)
  • 40. miR-106a-mediated malignant transformation of cells induced by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide. (nih.gov)
  • Additionally, moringa can upregulate caspase 3 and 9, which are associated with programmed cell death in cancer cells. (naturalnews.com)
  • Circulating EPO in the normal adult is mainly mass is made up of carbohydrate chains that produced by fibroblast-like interstitial cells of the renal cortex [9]. (who.int)
  • Carcinogenesis 2012 Sep 33 (9): 1699-706. (cdc.gov)
  • Using an established in vivo model of Fas-mediated apoptosis, we demonstrate here that elimination of certain caspases was compensated in vivo by the activation of other caspases. (cshl.edu)
  • Our findings provide direct experimental evidence for compensatory pathways of caspase activation. (cshl.edu)
  • Organic solvent-induced proximal tubular cell toxicity via caspase-3 activation. (cdc.gov)
  • Inhibiting ROCK-1 and caspases activation attenuated the MeHg-induced cell death. (nih.gov)
  • 14. Activation and substrate specificity of caspase-14. (nih.gov)
  • Collectively, these results suggest that p53-dependent and caspase-dependent induction of p38 MAPK directly participates in apoptosis induced by oridonin. (spandidos-publications.com)
  • A long pro-domain caspase that contains a CASPASE RECRUITMENT DOMAIN in its pro-domain region. (nih.gov)
  • Indeed, as early as the 1970s, investigators conducting research on the efficacy of RT in mouse tumor models observed reduced efficacy in immunodeficient nude mice compared to immunocompetent mice 9 pointing to a role for the adaptive immune response in the efficacy of RT. (nature.com)
  • In studies of mice, the Troy lab discovered that when blood vessels are injured by retinal vein occlusion, caspase-9 becomes uncontrollably activated, triggering processes that can damage the retina. (nih.gov)
  • Caspase polymorphisms and genetic susceptibility to multiple myeloma. (cdc.gov)
  • Caspase 9 promoter polymorphisms confer increased susceptibility to breast cancer. (cdc.gov)
  • Relative expression of caspase 3 and 9 proteins was obtained by real-time PCR. (ac.ir)
  • Expression of caspase-9 also increased within the first 3 h of infection, but subsequently decreased. (cdc.gov)
  • La caspasa 9 es activada durante el estrés celular por factores proapoptóticos derivados de las mitocondrias y por PROTEÍNAS ADAPTADORAS DE SEÑALIZACIÓN CARD como el FACTOR APOPTÓTICO 1 ACTIVADOR DE PROTEASAS. (bvsalud.org)
  • d , The cell lysates were assayed for caspase-9-like activity, and the pcDNA3.1-transfected cell lysate was used as the negative control. (cdc.gov)
  • In this project, a luciferase-based biosensor for detecting and measuring caspase-9 activity is designed and constructed using the circular permutation strategy. (caltech.edu)
  • Afterward, the biosensor is utilized for measuring the cellular caspase-9 activity upon apoptosis induction in a cancer cell line. (caltech.edu)
  • The obtained results show that the designed biosensor detects the caspase-9 activity in the cell-free and cell-based systems. (caltech.edu)
  • This newly discovered mechanism of NSAID activity suggests future studies into how these drugs affect caspases in the human body. (nih.gov)
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009 Dec 27 (34): 5823-9. (cdc.gov)
  • Median survival for patients with locally advanced disease is 9-12 months, and for patients with metastatic disease, the median survival is 3-6 months. (spandidos-publications.com)
  • Polymorphisms in the CASPASE genes and survival in patients with early-stage non-small-cell lung cancer. (cdc.gov)
  • Prognostic Impact of Polymorphisms in the CASPASE Genes on Survival of Patients with Colorectal Cancer. (cdc.gov)
  • Nod-1 was found to bind to multiple caspases with long prodomains, but specifically activated caspase-9 and promoted caspase- 9-induced apoptosis. (elsevierpure.com)
  • Corrigendum to "Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression" [Dev. (elsevierpure.com)
  • Caspases are known to play a role in inflammatory diseases such as rheumatoid arthritis and heart disease. (nih.gov)
  • Anxiety, depression, and delirium all negatively influence recovery after stroke ( 9 , 10 ). (frontiersin.org)
  • According to the World Health Organization , more than 9 million people worldwide die from cancer every year , making it the second leading cause of death after cardiovascular disease. (naturalnews.com)
  • Polymorphisms in the caspase genes and the risk of lung cancer. (cdc.gov)
  • Further tests of 9 selected NSAIDs showed that all except aspirin inhibited multiple caspases. (nih.gov)
  • Development of an inducible caspase-9 safety switch for pluripotent stem cell-based therapies. (nih.gov)
  • International journal of colorectal disease 2011 Sep 26 (9): 1113-8. (cdc.gov)
  • Caspase-9 and caspase3 were also induced by the silica treatment. (cdc.gov)